Treatment for skin disorders

ABSTRACT

Use of γ-linolenic acid and related materials alone or with zinc or β-lactam antibiotics to treat skin disorders.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation-in-part of my earlier copendingapplication Ser. No. 89,293 filed Oct. 30, 1979, now U.S. Pat. No.4,302,447, which in turn is a continuation-in-part of my earlierapplication Ser. No. 4,924 filed Jan. 19, 1979, now U.S. Pat. No.4,273,763.

FIELD OF THE INVENTION

This invention relates to the treatment of skin disorders primarily, butnot exclusively, in the field of human medicine.

GENERAL BACKGROUND

Considerable interest has been shown in recent years in the use ofprostaglandin (PG) precursors in medicine.

For various reasons it is not practical to administernaturally-occurring prostaglandins such as PGE 1 and PGE 2 to patients.Consequently, considerable attention has focussed on the use ofprostaglandin precursors including linoleic acid (9,12-octadecadienoicacid), γ-linolenic acid (6,9,12-octadecatrienoic acid) anddihomo-γ-linolenic acid (5,8,11-eicosatrienoic acid), conversion in thebody being believed to be as follows: ##STR1##

DESCRIPTION OF THE PRIOR ART

Prior art within this general area includes the following patents andpapers.

(i) U.S. Pat. Nos. 3,933,775 (issued Nov. 23rd, 1976) and 4,058,594(issued Nov. 15th, 1977) of John Williams, which describe a method ofproviding an immuno-suppressive effect in a patient undergoing organ ortissue transplant or suffering from multiple sclerosis comprisingadministration of a daily dosage of from 5 mg to 3 g of γ-linolenic acidor dihomo-γ-linolenic acid or a functional derivative thereof.

(ii) British Patent Specification No. 1,082,624, published Sept. 6th,1967, (Calmic Limited), which discloses effectiveness of γ-linolenicacid in the treatment of vascular diseases.

(iii) McCormack, Neil and Sim (The Lancet, page 508, Sept. 3rd, 1977),who describe preliminary work on the use of an oil containing a mixtureof linoleic acid and γ-linolenic acid (as triglycerides) in thetreatment of rheumatoid arthritis.

(iv) Sim and McCraw (Thrombosis Research Volume 10, pages 385-397.1977), who describe activity of the methyl esters of γ-linolenic acidand dihomo-γ-linolenic acid in vitro and in vivo on blood plateletfunction in non-human primates and in man.

(v) French Patent Specification No. 2 272 684 (Ito), which disclosesenhancement of antibiotic action by sundry unsaturated fatty acidsincluding [α-] linolenic acid.

PRESENT INVENTION

The present inventor has discovered a number of new applications ofγ-linolenic acid and dihomo-γ-linolenic acid in therapy, alone and inconjunction with zinc, β-lactam antibiotics or other materialsinfluencing the 1-series/2-series PG balance in the body in favour of1-series PG's, herein referred to as 1-series PG enhancers and fullydiscussed later. These applications are to skin disorders as set out indetail herein.

The present inventor believes that these disorders are due to adeficiency of PGE 1 and other PG's of the 1-series, or an imbalance inthe normal ratio of 1-series and 2-series PG's.

This has led to the realisation that the precursor(s) which can be usedto stimulate the natural production of 1-series PG's in the treatment ofthe disorders include γ-linolenic acid and/or dihomo-γ-linolenic acid,either or both of which may be used in association with linolenic acidand if desired other fat acids. Although these substances are 2-seriesPG precursors (via arachidonic acid) as well as 1-series PG precursors,this is not deleterious to their use, although one may require to userelatively higher amounts of precursors than would be the case if only1-series PG's were being biosynthesized.

Accordingly there is provided a method of treating skin disorders in apatient which comprises administering to the patient an effective amountof γ-linolenic acid and/or dihomo-γ-linolenic acid, optionally inassociation with linolenic acid and if desired other fat acids, saidacids being used, if desired, as physiologically functional derivativesthereof and optimally with a conjoint amount of a 1-series PG enhanceras referred to above.

A preferred daily dosage for an adult (weight ca 75 kg) is from 0.05 or0.1 up to 1, 2, 5 or even 10 g as required of γ-linolenic acid orequivalent weight (calculated as γ-linolenic acid) or physiologicallyfunctional derivative thereof. Amounts may in particular be 0.1 to 1.0 gdaily. In place of, or in addition to, γ-linolenic acid, one may usedihomo-γ-linolenic acid or a physiologically functional derivativethereof, in amounts equivalent in molar terms to γ-linolenic acid andcalculated as such. This dosage can for example be taken as a singledose or divided into 2, 3 or 4 subdivisions thereof as convenient.

ANTIBIOTICS

β-lactam antibiotics which may be used in the method of the presentinvention, are conveniently any of the known penicillin andcaphalosporin antibiotics (including semi-synthetic antibiotics) suchas, for example, penicillin G, penicillin N, penicillin V, cephalexin,cephalothin, ampicillin, amoxycillin, cloxacillin and caphaloglycin. Anyof these may be used in the form of their physiologically functionalnon-toxic derivatives, for example alkali metal salts e.g. sodium andpotassium salts, and salts with organic bases, and reference to anantibiotic herein (including the claims) includes reference to suchderivatives.

The antibiotics may for example be administered orally, parenterally orrectally as desired.

The antibiotic is preferably administered in the form of dosage units.Suitable daily dosages of said active ingredient may for example be inthe range 0.5 to 3.0 g per day in patients of average weight. Such dailydosages may conveniently be divided into for example, two, three or fourequal doses to be administered two, three or four times dailyrespectively.

The use of penicillins in long term treatment is especially desirable inview of the known relative absence of side effects of these drugs. Thus,penicillin has been administered for many years to patients havingrheumatic heart disease in order to prevent streptococcal infections,and there is virtually no evidence of long term toxicity.

Care should of course be taken to ensure that the patient is notallergic to the drug of choice.

If it is not desired to have compositions comprising both a 1-series PGenhancer and the γ-linolenic or other acid or derivatives, the activematerials may be given by separate administration in the appropriaterelative amounts.

SKIN DISORDERS

The skin disorders referred to include psoriasis, acne, dandruff,eczema, ichthyosis, scleroderma and hair loss (other than that due toinherited male pattern baldness).

The physiological basis for the invention is not understood in detailbut it is believed by the present inventor that conditions such aspsoriasis, dandruff, eczema, ichthyosis, scleroderma and hair loss arerelated to each other by common, or at least related, defects in1-series PG precursor metabolism, expressing themselves in various waysin different individuals. Experimental evidence of a relation isdiscussed below in the section on veterinary application of theinvention.

DIETARY COMPOSITIONS

The invention is chiefly described in terms of pharmaceuticalcompositions, but it will be understood that the γ-linolenic and otheracids, being in the nature of dietary supplements, could if available atan economic price to incorporated in a dietary margarine or otherfoodstuff; such foodstuffs are also referred to herein as dietarycompositions.

VETERINARY APPLICATIONS

It will be understood that where a disorder of a kind calling fortreatment in animals arises, the invention while described primarily interms of human medicine and treatment is equally applicable in theveterinary field.

Thus for example domestic cats have an unusual dietary requirement inessential fatty acids, being apparently unable to convert linoleic acidto γ-linolenic acid and dihomo-γ-linolenic acid to arachidonic acid.They are liable to a group of related skin conditions with hair loss,dandruff, scaling, pruritis, easy breakdown of the skin with rubbing orscratching, and defective healing, all of which can also be producedexperimentally by an EFA (essential fatty acid) deficient diet,evidencing their related nature. Similar conditions can be producedexperimentally in other animals, with skin lesions similar to eczema andpsoriasis. Feeding of γ- or dihomo-γ-linolenic acid is effective inreversing the conditions, including, perhaps surprisingly, those incats. This indicates, in view of the arachidonic acid block, that theconditions are indeed, as the present inventor believes also for thehuman skin conditions discussed above, related to 1 series PGdeficiencies. The spontaneous conditions observed in cats are forexample relieved by giving 0.5 g of Oenothera oil per day, five days aweek.

FORMS AND SOURCES OF γ-LINOLENIC AND OTHER ACIDS

Convenient physiologically functional derivatives of γ-linolenic acid ordihomo-γ-linolenic acid for use according to the invention for all thepurposes described include the C₁ -C₄ alkyl (e.g. methyl and ethyl)esters and the glycerides of the acids.

If desired, pharmaceutical compositions may be produced for use in theinvention by associating natural or synthetic γ-linolenic acid (or aphysiologically functional derivative thereof) and/or dihomo-γ-linolenicacid (or a physiologically functional derivative thereof) as such, withan acceptable pharmaceutical vehicle. It will however generally beconvenient to incorporate the γ-linolenic acid into compositions in theform of an available oil having a high γ-linolenic acid content.

At the present time known natural sources of oils having a highγ-linolenic acid content are few (there are no known natural sources ofsignificant amounts of dihomo-γ-linolenic acid). One source of oilscurrently available is the seed of Evening Primrose species such asOenothera biennis L. and Oenothera lamarckiana, the oil extracttherefrom containing γ-linolenic acid and linoleic acid in the form oftheir glycerides together with other glycerides. Another source ofγ-linolenic acid is the seed of Borage species such as Boragoofficinalis which, though its current yield per acre is low, provides aricher source of γ-linolenic acid than Oenothera oil. Recent studies onfungi which can be cultivated by fermentation promise a fungal oilsource.

The seed oil extracts referred to above can be used as such or can ifdesired be fractionated to yield an oily composition containing thetriglycerides of γ-linolenic acid and linoleic acid as the only fattyacid components, the γ-linolenic acid content being a major proportion.Seed oil extracts appear to have a stabilising effect upon anydihomo-γ-linolenic acid or physiologically functional derivative thereofincorporated therein.

USE OF 1-SERIES PG ENHANCERS GENERALLY AND ZINC IN PARTICULAR

As has been mentioned above, γ-linolenic acid and dihomo-γ-linolenicacid function as precursors for both 1- and 2-series PG's. The presentinventor believes it advantageous if the biosynthesis of 1-series PG'scan be effected preferentially to that of 2-series PG's in manyconditions in which 1-series PG imbalances or lack need to be corrected.

It has previously been believed that selective enhancement of 1-seriesPG formation and inhibition of 2-series PG formation are impossiblebecause the mobilisation of DGLA reserves and the mobilisation of AAreserves have been thought to be the same reaction, mediated by the samephospholipase. Similarly the formation of 1-series endoperoxides fromDGLA, leading to 1-series PG's has been thought inseparable from theformation of 2-series endoperoxides from AA, leading to 2-series PG's.The inventor however has evidence that these assumptions are not trueand that agents may be found which regulate the reactions selectively;for example penicillin and zinc appear to activate DGLA mobilisationwithout effecting AA mobilisation and the formation of 1-series PG's isincreased preferentially.

Most broadly, agents effective according to the invention are thosewhich:

(a) selectively activate DGLA mobilisation or conversion toendoperoxides, with small or no effect on AA mobilisation or conversion;

(b) inhibit conversion of DGLA to AA. (The body can make up any lack ofAA from reserves to maintain 2-series PG production if required);

(c) selectively inhibit AA mobilisation or conversion to endoperoxides,with small or no effect on DGLA mobilisation or conversion.

The materials referred to earlier herein as '1-series PG enhancers' thatis to say materials influencing the 1-series/2-series PG balance in thebody in favour of 1-series PG's, are thus believed to act by one or moreof the above mechanisms.

ZINC

Without restriction to the theory, the present inventor believes thatzinc is an example of materials that tend to stimulate the biosynthesisof 1-series PG's and specifically that it potentiates mobilisation ofesterified reserves of dihomo-γ-linolenic acid. This enables one to usezinc conjointly with γ-linolenic acid and/or dihomo-γ-linolenic acid.

Based on present evidence, a suitable daily dosage of zinc for an adult(weight ca 75 kg) is 2.5-800 mg preferably 10-200 mg and advantageously10-80 mg zinc daily, with γ-linolenic acid or other acid or equivalentin the amounts previously discussed. The 10-80 mg zinc is approximately0.125-1.0 mg/kg adult body weight. In view of the conjoint effect of thezinc preferred amounts of γ-linolenic or other acid or equivalent areless than when zinc is not present, advantageously 0.1 to 1.0 g daily.As before the dosage can be taken as a single dose or divided into 2, 3or 4 subdivisions thereof.

Conveniently the zinc or other 1-series PG enhancer and the γ-linolenicor other acid or derivatives are given together in a single preparationbut they can of course be taken separately.

Zinc should be administered in a form in which it is readily taken up invivo. Ordinarily this will indicate the use of a zinc salt of a mineralor organic acid, said salt being physiologically acceptable at the givendosage. Some zinc salts which would be contra-indicated at higherdosages may be satisfactory for present purposes at the dosagesindicated above. Useful salts include zinc sulphate and zinc gluconateand in particular zinc oleate, γ-linolenate and dihomo-65 -linolenate,and zinc oxide may also be employed. It is also possible to administerthe zinc in chelated form. In any event, the preferred amounts of zincare as stated above (the quantities given being calculated as zincmetal).

USE OF β-LACTAM ANTIBIOTICS

The use of γ-linolenic or other acids and derivatives, with β-lactamantibiotics, is discussed above. The present inventor believes that thereason for the effectiveness of the antibiotics is that, as he believeswith zinc, they enhance utilisation of ester reserves ofdihomo-γ-linolenic acid. Whether or not this is so, and no restrictionto the theory is intended, zinc and antibiotics do appear to haveparallel effects in treating all the conditions discussed herein whenused with the γ-linolenic or other acids and derivatives. Thecompositions may further be expected to be effective in the methods oftreatment described in the prior patents and other publications referredto.

It is also, further possible and has been found valuable to use bothzinc and β-lactam antibiotic conjointly with the γ-linolenic acid,dihomo-γ-linolenic acid or derivatives as described earlier.

In all cases the amounts of active materials are as discussed alreadyand association of the γ-linolenic or other acid with linolenic or otherfat acids is possible.

Methods of treatment with the addition of an effective conjoint amountof β-lactam antibiotic, particularly penicillin V, with or without zincare thus all within the invention, and the β-lactam antibiotics may ofcourse be used with additional 1-series PG enhancers other than zinc.

PHARMACEUTICAL PRESENTATION

The compositions as administered are conveniently in oral, rectal,parenteral or topical form in a suitable pharmaceutical vehicle, asdiscussed in detail for example in U.K. Patent Specification No. 1 082624 and in any case known generally according to the type ofpreparation. Thus for example tablets, capsules, ingestible liquid orpowder preparations, creams and lotions for topical application, orsuppositories, can be prepared as required.

Advantageously a preservative such as α-tocopherol is incorporated intothe preparations. α-Tocopherol in a concentration of about 0.1% byweight has been found suitable for the purpose.

It will be understood that the absolute quantity of active ingredientspresent in any dosage unit should not exceed that appropriate to therate and manner of administration to be employed but on the other handshould also desirably be adequate to allow the desired rate ofadministration to be achieved by a small number of doses. The rate ofadministration will moreover depend on the precise pharmacologicalaction desired.

The following Examples serve to illustrate the invention:

EXAMPLES

Pharmaceutical compositions containing a unit dose of an oil extractfrom the seeds of Oenothera biennis L. optionally with methyldihomo-γ-linolenate and/or zinc sulphate and/or penicillin V areprepared by encapsulation of the natural oil in soft gelatin capsulesmanufactured by known methods.

The oil is extracted from the seeds by one of the conventional methodsof extraction such as cold pressure, screw pressure after partiallycooking the seed, or solvent extraction.

Fractionation of a typical sample of this oil shows a yield of 97.0% oilin the form of methyl esters, with the relative proportions:

    ______________________________________                                               Palmitate 6.15                                                                Stearate  1.6                                                                 Oleate    10.15                                                               Linoleate 72.6                                                                γ-Linolenate                                                                      8.9                                                          ______________________________________                                    

As preservative, α-tocopherol is added to the oil in a concentration of0.1%.

Gelatin capsules containing oil extracts prepared as described above,each having the following contents of active ingredients (0.5 g oilextract=ca 0.045 g γ-linolenic acid), are prepared in conventionalfashion. The zinc may conveniently be incorporated as zinc oleate madeby the method disclosed in Monatschrift 42 287 (1921) and similarmethods may be applied to make for example zinc γ-linolenate if desired.

EXAMPLES, SKIN DISORDERS Example 1

    ______________________________________                                               Oil extract    0.5 g                                                          Zinc sulphate  10 mg                                                   ______________________________________                                    

Two capsules may be administered thrice daily in the treatment ofpsoriasis or the other skin disorders named herein, giving a daily doseof γ-linolenic acid of ca 0.27 g. Capsules without zinc are analternative.

Example 2

    ______________________________________                                        Oil extract              0.5 g                                                Methyl dihomo-γ-linolenate                                                                       10 mg                                                Zinc sulphate            10 mg                                                ______________________________________                                    

Two capsules may be administered thrice daily in treatments as inExample 1, capsules without zinc being an alternative.

Example 3

    ______________________________________                                               Oil extract    0.5 g                                                          Penicillin V   0.25 g                                                  ______________________________________                                    

Two capsules may be administered thrice daily in treatments as inExample 1.

Example 4

    ______________________________________                                               Oil extract    0.5 g                                                          Penicillin V   0.25 g                                                         Zinc sulphate  10 mg                                                   ______________________________________                                    

Two capsules may be administered thrice daily in treatments as inExample 1.

Example 5

    ______________________________________                                        Oil extract              0.5 g                                                Methyl dihomo-γ-linolenate                                                                       10 mg                                                Penicillin V             0.25 g                                               Zinc sulphate            10 mg                                                ______________________________________                                    

Two capsules may be administered thrice daily in treatments as inExample 1.

Example 6

    ______________________________________                                               Oil extract    0.5 g                                                   ______________________________________                                    

Two capsules may be administered thrice daily in the treatment of acne.

Example 7

    ______________________________________                                               Oil Extract    0.5 g                                                          Zinc sulphate  20 mg                                                   ______________________________________                                    

Two capsules may be administered thrice daily in the treatment of acne.

Example 8

    ______________________________________                                               Oil extract    0.5 g                                                   ______________________________________                                    

Two capsules may be administered thrice daily in the treatment ofpsoriasis.

Example 9

    ______________________________________                                               Oil Extract    0.5 g                                                          Zinc sulphate  20 mg                                                   ______________________________________                                    

Two capsules may be administered thrice daily in the treatment ofpsoriasis.

Example 10

    ______________________________________                                               Oil extract    0.5 g                                                   ______________________________________                                    

Two capsules may be administered thrice daily in the treatment ofeczema.

Example 11

    ______________________________________                                               Oil Extract    0.5 g                                                          Zinc sulphate  20 mg                                                   ______________________________________                                    

Two capsules may be administered thrice daily in the treatment ofeczema.

Example 12

    ______________________________________                                               Oil extract    0.5 g                                                   ______________________________________                                    

Two capsules may be administered thrice daily in the treatment anddandruff and loss of hair.

Example 13

    ______________________________________                                               Oil Extract    0.5 g                                                          Zinc sulphate  20 mg                                                   ______________________________________                                    

Two capsules may be administered thrice daily in the treatment ofdandruff and loss of hair.

EVIDENCE, TREATMENT OF SKIN DISORDERS

Acne and psoriasis are two common and intractable conditions that haveshown favourable results with treatment according to the invention.

Two groups of sufferers from severe acne, of 8 and 7 young menrespectively, received Oenothera oil 0.6 ml and Oenothera oil 0.6ml+zinc sulphate 20 mg, 6 capsules daily. All showed improvement interms of reduction both in the number of inflamed facial pustules and insebum production rate, over a period of 4 to 6 weeks, the group withzinc showing a greater improvement than the group without.

After three months all the subjects showed a very substantialimprovement, most being essentially clear of pustules.

A group of 4 subjects with psoriasis was given similar treatment. Inall, scaliness and itching were reduced, a group of three without zincinitially showing less improvement than a like group with, but catchingup when changed to the capsules with zinc. In no case was there a fullcure, but psoriasis is a particularly intractable condition in whicheven a modest improvement is clinically significant.

No clinical trials have been done on hair loss, but in a group of 30laboratory rats maintained on a zinc deficient diet, hair loss wasreversed by feeding of Oenothera oil with an increased effect when zincwas fed as well.

Preliminary results with eczema using Oenothera oil and zinc togetherhave given favourable indications, as found with psoriasis. Dandruffalso responded favourably in two individuals otherwise wholly healthy.

Further, a specific, double-blind, placebo controlled trial of the oilin a group of 14 children and 15 adults with severe atopic eczema hasgiven significant improvement in skin condition (Lovell, Burton andHorrobin, Lancet January 31st, 1981).

EXPERIMENTAL BACKGROUND, USE OF ZINC

Substantial clinical results are not at present available on all theconditions for which the use of zinc is proposed, but the presentinventor believes, without wishing to be limited to the theory, that atthe root of all the conditions lies a fault in prostaglandin metabolismwhereby PG's of the 1-series are lacking or their balance with 2-seriesPG's is upset. From evidence such as that listed below the inventorbelieves that zinc increases formation of 1-series PG's selectively,apparently by mediating the mobilisation from ester resources ofdihomo-γ-linolenic acid.

Thus zinc is indicated in all the conditions described herein, asfavouring 1-series PG synthesis specifically from administeredγ-linolenic acid and related materials.

In one group of experiments the test preparation was the isolatedsuperior mesenteric vascular bed, taken from male rats as for exampledescribed in the Canadian J. Physiol Pharmacol 54: 357, 1976. Theperfusion flow rate was at a constant value between 3 to 4 ml/min.,pressure 25 to 30 mm Hg, using Krebs bicarbonate buffer containing in nM150 Na, 4.3 K, 1.0 Mg, 2.5 Ca, 1.7 phosphate, 25 bicarbonate and 11.1glucose.

Prior to testing the basic vasoconstrictive effect of norepinephrine, asthe bitartrate, in successive 10 ng amounts was established, as theamplitude of a transient rise of about 1 min in the perfusion pressure.

Zinc, as the chloride, was then added to the perfusion buffer atsuccessive concentrations and the norepinephrine response measured after15 minutes at each.

The following results were obtained.

    ______________________________________                                        Zinc concentration                                                                            Response as %                                                 (μg/ml)      of basic level                                                ______________________________________                                        0.1             112                                                           0.2             118                                                           0.4             130                                                           0.8             138                                                           ______________________________________                                    

In the presence of 50 μg/ml of indomethacin, a known blocking agent forPG synthesis, used with 10 ng/ml PGE 2 to give apparently normalvascular reactivity, the zinc had no effect on the norepinephrineresponse.

Similar tests with dihomo-γ-linolenic acid and PGE 1 gave respectiverises up to a maximum of 130% of the basic response at 50 ng/ml of theacid and a maximum of 150% of the basic response at 2.8×10⁻¹¹ M PG.

The results show that zinc gives responses like those ofdihomo-γ-linolenic acid and of PGE 1, represents moreover which are notgiven when PG synthesis is blocked and PGE 2 is supplied, and thus thatconditions treated with γ-linolenic acid (and thus effectively withdihomo-γ-linolenic acid) may be enhanced in the direction of 1-series PGsynthesis by the addition of zinc.

BACKGROUND USE OF ANTIBIOTICS

On tests carried out as above, both penicillin V and penicillin G havegiven responses similar in kind and degrees to those given for zinc,supporting further inventor's belief that β-lactam antibiotics are ofvalue in conditions treated according to the invention in similar way tothe action of zinc.

I claim:
 1. A method of treating psoriasis, acne, dandruff, eczema,ichthyosis or scleroderma comprising administering to a person sufferingtherefrom an effective amount of from about 0.05 to about 10 g(calculated as γ-linolenic acid) daily of γ-linolenic acid orphysiologically functional derivative thereof and/or dihomo-γ-linolenicacid or physiologically functional derivative thereof.
 2. A methodaccording to claim 1, wherein the daily amount of γ-linolenic ordibromo-γ-linolenic acid or derivatives thereof is from 0.1 to 5 gcalculated as γ-linolenic acid.
 3. A method of treating psoriasis, acne,dandruff, eczema, ichthyosis or scleroderma comprising administering toa person suffering therefrom an effective amount of (a) γ-linolenic acidor physiologically functional derivative thereof and/ordihomo-γ-linolenic acid or physiologically functional derivative thereofin an amount of from about 0.05 to about 10 g (calculated as γ-linolenicacid) daily, and (b) an effective conjoint amount of a materialinfluencing the 1-series/2 series PG balance in the body in favour of1-series PG's.
 4. A method according to claim 4, wherein said material(b) is physiologically assimilable zinc.
 5. A method according to claim4, wherein the daily amount of said zinc is from about 2.5 to about 800mg.
 6. A method according to claim 4, wherein the daily amount of theactive components is from 0.1 to 5 g of (a) calculated as γ-linolenicacid and from 10 to 80 mg of (b).
 7. A method according to claim 3,wherein said material (b) is a β-lactam antibiotic.
 8. A methodaccording to claim 7, wherein said antibiotic is a natural orsemi-synthetic penicillin or cephalosporin antibiotic.
 9. A methodaccording to claim 7, wherein said antibiotic is selected frompenicillin G, penicillin N, penicillin V, cephalothin, ampicillin,amoxycillin, cloxacillin, cephalexin and cephaloglycin.
 10. A methodaccording to claim 7, 8 or 9 wherein the daily amount of said component(b) is from about 0.5 to about 3 g.
 11. A method according to claim 7, 8or 9, wherein the daily amount of the active components is from 0.1 to 5g of (a) calculated as γ-linolenic acid and from 0.5 to 3 g of (b). 12.A method of treating psoriasis, acne, dandruff, eczema, ichthyosis orscleroderma comprising administering to a person suffering therefrom aneffective amount of (a) γ-linolenic acid or physiologically functionalderivative thereof and/or dihomo-γ-linolenic acid or a physiologicallyfunctional derivative thereof in an amount of about 0.05 to about 10 g(calculated as γ-linolenic acid) daily and conjoint amounts of (b)physiologically assimilable zinc of about 2.5 to about 800 mg daily, and(c) from about 0.5 to about 3 g of a β-lactam antibiotic daily.
 13. Amethod according to claim 4 or 12 wherein the zinc is present as zincoleate, zinc γ-linolenate or zinc dihomo-γ-linolenate.